Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis
In: Autophagy Autophagy, 2015, 11 (7), pp.1130-1145. ⟨10.1080/15548627.2015.1049799⟩ Autophagy, Taylor & Francis, 2015, 11 (7), pp.1130-1145. ⟨10.1080/15548627.2015.1049799⟩; (2015-07-01)
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International audience; The glomerulus is a highly specialized capillary tuft, which under pressure filters large amounts of water and small solutes into the urinary space, while retaining albumin and large proteins. The glomerular filtration barrier (GFB) is a highly specialized filtration interface between blood and urine that is highly permeable to small and midsized solutes in plasma but relatively impermeable to macromolecules such as albumin. The integrity of the GFB is maintained by molecular interplay between its 3 layers: the glomerular endothelium, the glomerular basement membrane and podocytes, which are highly specialized postmitotic pericytes forming the outer part of the GFB. Abnormalities of glomerular ultrafiltration lead to the loss of proteins in urine and progressive renal insufficiency, underlining the importance of the GFB. Indeed, albuminuria is strongly predictive of the course of chronic nephropathies especially that of diabetic nephropathy (DN), a leading cause of renal insufficiency. We found that high glucose concentrations promote autophagy flux in podocyte cultures and that the abundance of LC3B II in podocytes is high in diabetic mice. Deletion of Atg5 specifically in podocytes resulted in accelerated diabetes-induced podocytopathy with a leaky GFB and glomerulosclerosis. Strikingly, genetic alteration of autophagy on the other side of the GFB involving the endothelial-specific deletion of Atg5 also resulted in capillary rarefaction and accelerated DN. Thus autophagy is a key protective mechanism on both cellular layers of the GFB suggesting autophagy as a promising new therapeutic strategy for DN.
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Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis
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Autor/in / Beteiligte Person: | Flosseau, Kathleen ; Guyonnet, Léa ; Huber, Tobias B. ; Bensaada, Imane ; Tharaux, Pierre-Louis ; Schmitt, Alain ; Jasiek, Magali ; Chipont, Anna ; Lenoir, Olivia ; Bork, Tillmann ; Hartleben, Björn ; Hénique, Carole ; Souyri, Michèle ; Jean Marc Massé ; Laboratoire de Biologie du Développement (LBD) ; Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS) ; Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) ; INSERM, Joint Transnational Call 2011 for ``Integrated Research on Genomics and Pathophysiology of the Metabolic Syndrome and the Diseases arising from it' from l'Agence Nationale de la Recherche (ANR) of France ; Fondation de France ; Region Ile-de-France (CORDDIM) ; Societe Francophone du Diabete (SFD) ; German Research Foundation DFG [KFO 201] ; DFG (Heisenberg program) [CRC 992] ; European Research Council (ERC) ; Excellence Initiative of the German Federal and State Governments |
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Quelle: | Autophagy Autophagy, 2015, 11 (7), pp.1130-1145. ⟨10.1080/15548627.2015.1049799⟩ Autophagy, Taylor & Francis, 2015, 11 (7), pp.1130-1145. ⟨10.1080/15548627.2015.1049799⟩; (2015-07-01) |
Veröffentlichung: | HAL CCSD, 2015 |
Medientyp: | unknown |
ISSN: | 1554-8627 (print) ; 1554-8635 (print) |
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